edoc

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Burri, Christian and Yeramian, Patrick D. and Allen, James L. and Merolle, Ada and Serge, Kazadi Kyanza and Mpanya, Alain and Lutumba, Pascal and Mesu, Victor Kande Betu Ku and Bilenge, Constantin Miaka Mia and Lubaki, Jean-Pierre Fina and Mpoto, Alfred Mpoo and Thompson, Mark and Munungu, Blaise Fungula and Manuel, Francisco and Josenando, Théophilo and Bernhard, Sonja C. and Olson, Carol A. and Blum, Johannes and Tidwell, Richard R. and Pohlig, Gabriele. (2016) Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies. PLoS neglected tropical diseases, 10 (2). e0004362.

[img] PDF - Published Version
Available under License CC BY (Attribution).

1030Kb

Official URL: http://edoc.unibas.ch/42147/

Downloads: Statistics Overview

Abstract

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Medicine > Medical Consultations (Blum)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Medicine > Research Cluster (Burri)
UniBasel Contributors:Burri, Christian and Blum, Johannes A.
Item Type:Article, refereed
Publisher:Public Library of Science
ISSN:1935-2727
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:25 Aug 2016 10:26
Deposited On:28 Apr 2016 08:59

Repository Staff Only: item control page